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Screening of food factors that target the quality control system of mitochondria

Research Project

Project/Area Number 23658118
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Food science
Research InstitutionNagoya University

Principal Investigator

KAWAI Yoshichika  名古屋大学, 生命農学研究科, 准教授 (50380027)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsオートファジー / ポリフェノール / フラボノイド / ミトコンドリア / マクロファージ / 炎症 / 食品因子
Research Abstract

We screened the food factors that enhance the autophagic degradation leading to mitochondrial quality control. In HeLa cells, luteolin and the derivatives significantly enhanced the autophagic degradation of p62, an adaptor protein of autophagy. In contrast, in J774.1 macrophages, the mRNA expression of p62 was significantly enhanced upon treatment with flavonols such as quercetin, whereas no effects were observed upon treatment with luteolin derivatives. These results strongly suggest that the activities of polyphenols for autophagy induction are dependent on cell types. It was also found that p62 mRNA expression was enhanced through the activation of Nrf2, a transcription factor. Furthermore, the pretreatment of J774.1 with flavonols resulted in the decrease in both intracellular and extracellular IL-1beta, an autophagy substrate. These results suggest that autophagy induction by polyphenols might be good strategy for the quality control of intracellular proteins and organelles.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (32 results)

All 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 12 results,  Open Access: 1 results) Presentation (15 results) (of which Invited: 2 results) Remarks (3 results)

  • [Journal Article] Mitochondrial dysfunction leads to deconjugation of quercetin glucuronides in inflammatory macrophages2013

    • Author(s)
      Ishisaka, A., Kawabata, K., Miki, S., Shiba, Y., Minekawa, S., Nishikawa, T., Mukai, R., Terao, J., and Kawai, Y
    • Journal Title

      PLoS One

      Volume: 8 Issue: 11 Pages: e80843-e80843

    • DOI

      10.1371/journal.pone.0080843

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Non-specific protein modifications by a phytochemical induce heat shock response for self-defense2013

    • Author(s)
      Kohta Ohnishi
    • Journal Title

      PLoS One

      Volume: 8(3) Issue: 3 Pages: 1-15

    • DOI

      10.1371/journal.pone.0058641

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress2012

    • Author(s)
      Lee, I.H., Kawai, Y., Fergusson, M.M., Rovira, I.I., Bishop, A.J., Motoyama, N., Cao, L., and Finkel, T
    • Journal Title

      Science

      Volume: 336 Issue: 6078 Pages: 225-228

    • DOI

      10.1126/science.1218395

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bioavailability of orally administered water-dispersible hesperetin and its effect on peripheral vasodilatation in human subjects: implication of endothelial functions of plasma conjugated metabolites.2012

    • Author(s)
      Takumi, H., Nakamura, H., Simizu, T., Harada, R., Kometani, T., Nadamoto, T., Mukai, R., Murota, K., Kawai, Y., and Terao, J.
    • Journal Title

      Food and Function

      Volume: 3 Issue: 4 Pages: 389-398

    • DOI

      10.1039/c2fo10224b

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of quercetin and its glucuronide metabolite upon 6-hydorxydopamine-induced oxidative damage in Neuro-2a cells.2012

    • Author(s)
      Mukai, R., Kawabata, K., Otsuka, S., Ishisaka, A., Kawai, Y., Ji, Z.S., Tsuboi, H., and Terao, J.
    • Journal Title

      Free Radical Research

      Volume: 46 Issue: 8 Pages: 1019-1028

    • DOI

      10.3109/10715762.2012.673720

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Monoclonal antibody against protein-bound glutathione: use of glutathione conjugate of acrolein-modified proteins as an immunogen.2012

    • Author(s)
      Furuhata, A., Honda, K., Shibata, T., Chikazawa, M., Kawai, Y., Shibata, N., and Uchida, K.
    • Journal Title

      Chemical Research in Toxicology

      Volume: 25 Issue: 7 Pages: 1392-1401

    • DOI

      10.1021/tx300082u

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Quantitative analysis of acrolein-specific adducts generated during lipid peroxidation-modification of proteins in vitro: identification of N(τ)-(3-propanal)histidine as the major adduct.2012

    • Author(s)
      Maeshima, T., Honda, K., Chikazawa, M., Shibata, T., Kawai, Y., Akagawa, M., and Uchida, K.
    • Journal Title

      Chemical Research in Toxicology

      Volume: 25 Issue: 7 Pages: 1384-1392

    • DOI

      10.1021/tx3000818

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The ferroimmunomodulatory role of ectopic endometriotic stromal cells in ovarian endometriosis.2012

    • Author(s)
      Kobayashi H, Yamashita Y, Iwase A, Yoshikawa Y, Yasui H, Kawai Y, Uchida K, Uno N, Akatsuka S, Takahashi T, Kikkawa F, Toyokuni S.
    • Journal Title

      Fertil Steril

      Volume: 98 Issue: 2 Pages: 415-22

    • DOI

      10.1016/j.fertnstert.2012.04.047

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of quercetin and glucuronide metabolites on the monoamine oxidase-A reaction in mouse brain mitochondria2011

    • Author(s)
      Yoshino, S., Hara, A., Sakakibara, H., Kawabata, K., Tokumura, A., Ishisaka, A., Kawai, Y., and Terao, J.
    • Journal Title

      Nutrition

      Volume: 27 Pages: 847-852

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharmacology in health food: metabolism of quercetin in vivo and its protective effect against arteriosclerosis2011

    • Author(s)
      Ishizawa, K., Yoshizumi, M., Kawai, Y., Terao, J., Kihira, Y., Ikeda, Y., Tomita, S., Minakuchi, K., Tsuchiya, K., and Tamaki, T.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 115 Pages: 466-470

    • NAID

      10029893264

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats.2011

    • Author(s)
      Ishisaka, A., Ichikawa, S., Sakakibara, H., Piskula, M.K., Nakamura, T., Kato, Y., Ito, M., Miyamoto, K., Tsuji, A., Kawai, Y., and Terao, J.
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 51 Pages: 1329-1336

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Benzene Metabolite, 1,2,4-benzenetriol, induces halogenated DNA and tyrosines representing halogenative stress in human myeloid cell line HL-60.2011

    • Author(s)
      Nishikawa, T., Miyahara, E., Horiuchi, M., Izumo, K., Okamoto, Y., Kawai, Y., Kawano, Y., Takeuchi, T.
    • Journal Title

      Environmental Health Perspectives

      Volume: 120 Pages: 62-67

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunochemical Detection of Food-Derived Polyphenols in the Aorta: Macrophages as a Major Target Underlying the Anti-Atherosclerotic Activity of Polyphenols.2011

    • Author(s)
      Kawai, Y.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 75 Pages: 609-617

    • NAID

      10028271026

    • Related Report
      2011 Research-status Report
  • [Journal Article] Conjugated quercetin glucuronides as bioactive metabolites and precursors of aglycone in vivo.2011

    • Author(s)
      Terao, J., Murota, K., and Kawai, Y.
    • Journal Title

      Food and Function

      Volume: 2 Pages: 11-7

    • Related Report
      2011 Research-status Report
  • [Presentation] マクロファージとの相互作用を介したポリフェノール抱合体の活性制御機構2013

    • Author(s)
      河合慶親
    • Organizer
      第67回日本栄養・食糧学会大会
    • Place of Presentation
      名古屋
    • Year and Date
      2013-05-25
    • Related Report
      2013 Final Research Report
  • [Presentation] Flavonoids induce autophagic degradation : a possible mechanism for the health-beneficial effects of dietary flavonoids2013

    • Author(s)
      Yoshichika Kawai
    • Organizer
      13th International Conference of Functional Food Center (FFC)
    • Place of Presentation
      Kyoto(シンポジウム講演)
    • Year and Date
      2013-05-11
    • Related Report
      2013 Final Research Report
  • [Presentation] オートファジー誘導を介した抗炎症作用を有するポリフェノール類の探索2013

    • Author(s)
      坂下 友紀、額 惠理香、大西 康太、河合 慶親
    • Organizer
      第18回日本フードファクター学会(JSoFF)
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Flavonoids induce autophagic degradation: a possible mechanism for the health-beneficial effects of dietary flavonoids2013

    • Author(s)
      Yoshichika Kawai
    • Organizer
      13th International Conference of Functional Food Center (FFC)
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] New insights into the anti-inflammatory mechanisms of dietary flavonoids: involvement of mitochondrial dysfunction and autophagy2013

    • Author(s)
      Yoshichika Kawai
    • Organizer
      6th International conference on Polyphenol and Health (ICPH)
    • Place of Presentation
      ブエノスアイレス
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] LC-MS/MSによる過酸化脂質-DNA付加体の網羅解析及び検出系の確立2013

    • Author(s)
      河合慶親、額惠理香、柴田貴広、内田浩二
    • Organizer
      日本農芸化学会2013年度大会
    • Place of Presentation
      仙台
    • Related Report
      2012 Research-status Report
  • [Presentation] ミトコンドリア障害に起因するマクロファージ炎症応答機構の解析2012

    • Author(s)
      河合慶親, 川津英賢, 柴田貴広, 内田浩二
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      博多
    • Year and Date
      2012-12-15
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] フラボノイド類によるオートファジー誘導機構の解析2012

    • Author(s)
      石原朋恵, 寺尾純二, 柴田貴広, 内田浩二, 河合慶親
    • Organizer
      2012年度日本農芸化学会
    • Place of Presentation
      京都
    • Year and Date
      2012-03-23
    • Related Report
      2013 Final Research Report
  • [Presentation] 炎症部位における抗酸化ポリフェノールの機能性発現機構の解析2012

    • Author(s)
      河合慶親
    • Organizer
      日本酸化ストレス学会東海支部設立シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2012-02-18
    • Related Report
      2013 Final Research Report
  • [Presentation] フラボノイド類によるオートファジー誘導機構の解析2012

    • Author(s)
      石原朋恵、寺尾純二、柴田貴広、内田浩二、河合慶親:
    • Organizer
      日本農芸化学会2012年度大会
    • Place of Presentation
      京都女子大学(京都)
    • Related Report
      2011 Research-status Report
  • [Presentation] マクロファージにおけるポリフェノールの抗炎症作用機構の解析2012

    • Author(s)
      神原哲士、河合慶親、柴田貴広、内田浩二:
    • Organizer
      日本農芸化学会2012年度大会
    • Place of Presentation
      京都女子大学(京都)
    • Related Report
      2011 Research-status Report
  • [Presentation] 炎症部位における抗酸化ポリフェノールの機能性発現機構の解析2012

    • Author(s)
      河合慶親
    • Organizer
      日本酸化ストレス学会東海支部設立シンポジウム(招待講演)
    • Place of Presentation
      名古屋大学医学部(名古屋)
    • Related Report
      2011 Research-status Report
  • [Presentation] Prodrug-like actions of dietary polyphenols at the sites of inflammation2012

    • Author(s)
      Kawai, Y
    • Organizer
      The International Symposium on Food, Nutrition, and Vascular Function 2012(招待講演)
    • Place of Presentation
      徳島大学(徳島)
    • Related Report
      2011 Research-status Report
  • [Presentation] Toren Finkel : ミトコンドリア膜電位低下に伴うLC3-PE 複合体生成機構の解析2011

    • Author(s)
      河合慶親, 柴田貴広, 内田浩二
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2011-09-24
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリア膜電位低下に伴うLC3-PE複合体生成機構の解析2011

    • Author(s)
      河合慶親、柴田貴広、内田浩二、Toren Finkel
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都)
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.agr.nagoya-u.ac.jp/~food/

    • Related Report
      2013 Final Research Report
  • [Remarks] 名古屋大学大学院生命農学研究科食品機能化学研究室

    • URL

      http://www.agr.nagoya-u.ac.jp/~food/index.html

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.agr.nagoya-u.ac.jp/~food/index.html

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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